This proposal is a continuing request to study cyclization reactions leading to the formation of medium and large rings (8-16 members) by the generation of a new carbon-carbon bond. The palladium catalyzed coupling reaction of an organic electrophile with an organotin group is an ideal reaction for this construction since it is a fast, high yield reaction that takes place stereospecifically under mild conditions and tolerates a wide variety of functional groups. Thus a prime objective of this research is the development of the intramolecular cyclization of a molecule containing an organic electrophile and a vinyltin unit at the termini. A knowledge of the phosphine type as well as the preferred solvent is critical to designing a catalyst supported on a highly cross-linked polymer, the purpose of which is to optimize the intramolecular reaction and reduce the intermolecular oligomerization. Thus, another goal is the rational design of a polymer supported catalyst. It is also the purpose of this research to determine which electrophilic types and organotin partners will participate in the coupling to give high yields of cyclized products. Broadening the scope of the cyclization reaction, particularly to the coupling reactions of vinyl electrophiles with organostannanes, will permit the synthesis of a wider variety of products. Finally, a key objective is the utilization of these cyclization procedures in the synthesis of a variety of biologically active ring compounds. In particular the ring systems of the polyoxo-macrolides produced by streptomyces microorganisms such as methynolide (12-membered), ingramycin (14-membered), erythronolides and mycinolides, tylonolides, or carbonolides (16-membered) as well as the ring systems of the beta-resorcyclic acid macrolide group such as zearalenone (14-membered) or milbemycin beta3 are potential targets. The synthesis of an important new class of antitumor antibiotics containing the conjugated enediyne chromaphore to which neocarzinostatin, calichemicin and esperamicins belong is especially attractive, since these molecules are highly functionalized yet are unstable, particularly in the presence of nucleophiles.